Registry Study Confirms That Faster Thrombolysis Improves Stroke Outcomes

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The earlier stroke patients receive thrombolysis with tissue plasminogen activator (tPA), the better they fare in terms of in-hospital mortality and functional outcomes, according to the findings of a large national registry reflecting the diversity of US practice. Published in the June 19, 2013, issue of the Journal of the American Medical Association, the study confirms the conclusion of multiple clinical trials.

Investigators led by Jeffrey L. Saver, MD, of the University of California, Los Angeles, David Geffen School of Medicine (Los Angeles, CA), looked at 58,353 patients from 1,395 centers treated for acute ischemic stroke with IV tPA within 4.5 hours of symptom onset from April 2003 through March 2012. All patients were enrolled in the American Heart Association/American Stroke Association Get With the Guidelines-Stroke national registry.

Most Patients Treated 1.5 to 3 Hours After Symptom Onset

The median onset-to-treatment (OTT) time was 144 minutes, with three-quarters of patients (77.2%) falling within the range of 91 to 180 minutes. Of the remaining patients, 9.3% were treated within the first 90 minutes, while 13.2% received tPA between 181 and 270 minutes after symptom onset.

In multivariable analysis, the factors most strongly associated with shorter times to treatment were:

  • Greater stroke severity, per 5-point increase in National Institutes of Health Stroke Scale (NIHSS) score (OR 2.8; 95% CI 2.5-3.1)
  • Arrival by EMS (OR 5.9; 95% CI 4.5-7.3)
  • Arrival during ‘regular’ hours (OR 4.6; 95% CI 3.8-5.4)
  • Higher annual hospital volume of IV tPA cases, per 5-case increase (OR 1.6; 95% CI 1.1-2.2)

Longer OTT times were predicted by:

  • History of stroke/TIA (OR -3.0; 95% CI -2.1 to -3.9)
  • History of diabetes (OR -1.8; 95% CI -0.4 to -3.1)
  • History of peripheral vascular disease (OR -2.5; 95% CI -0.5 to -4.4)
  • Lower annual volume of hospital ischemic stroke admissions, per 50-case decrease (OR -1.2; 95% CI -0.7 to -1.7)
  • Hospital location in the South (OR -3.1; 95% CI -1.2 to -5.0) or Midwest (OR -3.2; 95% CI -1.2 to -5.4)

Race/ethnicity, hospital academic status, and rural vs. urban location of the hospital did not affect time to treatment.

Overall, 8.8% of patients died in the hospital and 4.9% suffered an intracranial hemorrhage, while 33.4% achieved independent ambulation at hospital discharge and 38.6% were discharged to home. Earlier administration of tPA, measured in 15-minute increments, was associated with improvements in each of these outcomes (table 1).

Table 1. Adjusted Outcomes, per 15-Minute Decrease in OTT Time

 

Adjusted OR

95% CIa

In-Hospital Mortality

0.96

0.95-0.98

Symptomatic Intracranial Hemorrhage

0.96

0.95-0.98

Independent Ambulation at Discharge

1.04

1.03-1.05

Discharge to Home

1.03

1.02-1.04

a P < 0.001 for each comparison.

A similar pattern was seen when tPA within the first 90 minutes was compared with treatment within the following 90 minutes, and treatment within the latter time frame was compared with treatment between 181 and 270 minutes.

Similarly, for every 15-minute-faster interval of treatment, patients were more likely to achieve better ambulatory status (ie, independent vs. assisted vs. nonambulatory; OR 1.04; 95% CI 1.03-1.05) and to be discharged to a more independent setting (ie, home vs. acute rehabilitation vs. skilled nursing facility; OR 1.03; 95% CI 1.03-1.04).

The researchers calculated that for every 1,000 patients treated, each 15-minute reduction in OTT time would result in 18 more patients with improved ambulation at discharge, 13 more discharged to a more independent environment, and 4 fewer deaths before discharge.

The association of shorter OTT time with improved outcomes was consistent across subgroups defined by age, sex, race/ethnicity, and presenting stroke severity.

Registry Supports Generalizability of Timely Treatment Benefit

In a telephone interview with TCTMD, Adnan Qureshi, MD, of the University of Minnesota Medical Center (Minneapolis, MN), said the study supports the generalizability of the time-to-treatment benefit “across almost all settings, as opposed to clinical trials, which represent more selected settings and more rigorous implementation plans, as dictated by the trial protocol.”

The study’s large size also enables a “more conclusive demonstration” of the reduction of mortality and intracranial hemorrhage with earlier thrombolysis that was suggested by clinical trials, he added.

Dr. Qureshi observed that the factors delaying time to treatment were not unexpected, explaining that the presence of comorbidities such as diabetes and peripheral vascular disease makes physician assessment more time-consuming and decision making more complex.

He called the absence of an interaction with certain hospital variables “validation of the effectiveness of 12 years of national efforts to incorporate time to treatment as a quality measure,” which engaged both physicians and hospital administrations. 

Treatment Window Not a “Comfort Threshold” 

The study authors say the results “support intensive efforts to accelerate patient presentation and to streamline regional and hospital systems of acute stroke care to compress OTT times.”

One thrust of such a campaign is aimed at public education, including knowledge of the signs of a stroke in progress and readiness to activate the emergency medical system. The other centers on improving regional organization of care to ensure recognition of stroke, high-priority transport of patients to certified stroke centers, and pre-arrival notification of stroke teams and readying of CT or MRI scanners for immediate use.

Dr. Qureshi agreed, highlighting that EMS delivery to the hospital shortens time to treatment--a fact that patients are often unaware of, he commented. “The message for physicians and hospitals,” he said, “is that while there is a 4.5-hour window for thrombolysis, the benefit is almost exponentially lost by the minute, so we shouldn’t take that as a comfort threshold.” 

 


Source:
Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:2480-2488.

 

 

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Registry Study Confirms That Faster Thrombolysis Improves Stroke Outcomes

The earlier stroke patients receive thrombolysis with tissue plasminogen activator (tPA), the better they fare in terms of in hospital mortality and functional outcomes, according to the findings of a large national registry reflecting the diversity of US practice. Published
Disclosures
  • Dr. Saver reports serving as a member of the Get With The Guidelines Science Subcomittee and as a consultant to Brainsgate, CoAxia, Covidien, Grifols, Lundbeck, and St. Jude Medical; and being an employee of the University of California, which holds a patent for retriever devices for stroke.
  • Dr. Qureshi reports no relevant conflicts of interest.

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